Luteinizing Hormone Releasing Hormone ("LHRH") is secreted by the hypothalamus and carried to the pituitary gland where it stimulates secretion of follicle stimulating hormone and luteinizing hormone which, in turn stimulate ovarian follicle development, the conversion of ovarian follicle to corpus luteum, tubule development in the testicles and production of progesterone and testosterone. Thus, release of LHRH causes ovulation and formation of corpus luteum in females and spermatogenesis in males.
LHRH is a decapeptide of the following structure: EQU pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH.sub.2
wherein, according to convention, the amino group of each amino acid appears to the left and the carboxyl to the right with the hydroxyl of the carboxyl of the terminal Gly being replaced by an NH.sub.2 group. The conventional abbreviations for the amino acids are: Glu (glutamic acid), pGlu (pyroglutamic acid), His (histidine), Trp (tryptophane), Ser (serine), Tyr (tyrosine), Gly (glycine), Leu (leucine), Arg (arginine), Pro (proline), Lys (lysine) and Cys (cysteine). Except for glycine which has no optical center, all amino acids are of the L-configuration unless otherwise indicated. LHRH may be produced as described in U.S. Pat. Nos. 4,159,980 and 4,213,895.
Analogues of LHRH have been prepared which act as agonists or antagonists of LHRH, i.e., which tend to diminish or accentuate the action of LHRH in the body. Such analogues are described in U.S. Pat. Nos. 3,880,825; 3,941,763; 4,034,082; 4,072,668; 4,075,192; 4,143,133; 4,143,136; 4,211,769; 4,234,571; and 4,263,282. These analogues may be administered to the animal or patient in amounts such as 2 to 200 micrograms per kilogram of body weight to yield an immediate effect on the reproductive cycle as described in U.S. Pat. No. 4,010,261. A second type of treatment is the administration to the patient or animal of an LHRH analogue as an antigen, i.e., immunogen, whereby the analogue acts as a vaccine and the host mammal generates antibodies to the analogue which also act against the body's own LHRH. Thus, the analogue's effect will persist after the analogue itself has been metabolized or excreted. This second treatment is described for various LHRH analogues or LHRH itself by A. Arimura et al. in Endocrinology 93:1092-1103 (1973); by H. M. Fraser et al. in the Journal of Endocrinology 63:399-406 (1974); by S. L. Jeffcoate et al. in Immunochemistry Vol. 11, p. 75-77 (1974); by I. J. Clarke et al. in the Journal of Endocrinology 78:39-47 (1978); by L. Pique et al. in Immunochemistry Vol. 15 pages 55-60 (1978); by V. C. Stevens et al. in the American Journal of Reproductive Immunology 1:307-314 (1981); and in U.S. Pat. No. 3,963,691.
An object of the present invention is a vaccine containing an immunogen which prevents the function of LHRH when administered to a male or female mammal. At present there are 43 million dogs and 31 million cats in the United States and their numbers increase daily. Stray dogs and cats along with wild animals such as skunks and raccoons are known to be major sources of rabies transmission to domestic animals and humans. Surgical removal of reproductive organs, e.g., spaying and castration, is presently a commonly used method for preventing reproduction in mammals. However, surgery is relatively costly, time consuming and impractical when used with wild or stray animals. A vaccine which immunizes the animal against its own LHRH would prevent conception for extended periods and would be a cost-effective method of population control. A further object is a vaccine form which can be used in dart-guns or drug-containing bullets for the immunization of wild mammals. An object of the invention is a vaccine for population control of a large population of animals such as deer, wild horses and burros and animals kept in zoos.
A further object of the invention is a vaccine containing an immunogen for the treatment of male mammals for the undesired effects of LHRH in such animals. For example, cryptorchidism is a condition where one or both testicles of a male mammal have not descended from the abdomen making castration a difficult surgical procedure. A vaccine which prevents LHRH from transmitting signals to produce male hormones would be, in effect, a "immunological castration" for male mammals and could be used to render cryptorchid stallions docile.